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| LETTER TO EDITOR |
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| Year : 2022 | Volume
: 5
| Issue : 1 | Page : 176-177 |
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Authors' reply to Jaiswal and Chanana
Ullas Batra1, Shrinidhi Nathany2, Himanshi Diwan2
1 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India
2 Department of Pathology (Molecular Diagnostics), Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India
| Date of Submission | 30-Jan-2022 |
| Date of Decision | 18-Feb-2022 |
| Date of Acceptance | 18-Feb-2022 |
| Date of Web Publication | 31-Mar-2022 |
Correspondence Address:
Ullas Batra
Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Center, Sector 5, Rohini, Sir Chhotu Ram Marg, New Delhi - 110 085
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/crst.crst_62_22
How to cite this article:
Batra U, Nathany S, Diwan H. Authors' reply to Jaiswal and Chanana. Cancer Res Stat Treat 2022;5:176-7 |
We appreciate the expository comments of Jaiswal and Chanana[1] on our article, “RET in non-small cell lung carcinoma: A narrative review.”[2] Rearranged during transfection (RET) gene rearrangements are described in 1%–2% of all non-small-cell lung carcinomas (NSCLCs), with KIF5B being the most common fusion partner.[3],[4] These are more often encountered in young, never-smoker patients with solid variants of adenocarcinoma. Although there is paucity of data predicting the outcome of this rare entity, few studies have emphatically reported that patients with NSCLC harboring RET fusion have worse prognosis.[3] With the approval of selpercatinib and pralsetinib, RET rearrangements joined the ranks of targetable molecular alterations in NSCLC.
We are in consensus with Jaiswal and Chanana that the LIBRETTO-001 and ARROW trials predominantly included pretreated RET-rearranged NSCLCs, with few treatment-naïve patients. However, the ARROW trial reported an objective response rate (ORR) of 73% in the treatment-naïve group (n = 29) compared to 61% in the pretreated group (n = 91).[5] The ongoing trials will better elucidate the ORR and progression-free survival (PFS) of treatment-naïve patients with RET-rearranged NSCLC. Meanwhile, the National Comprehensive Cancer Network has recommended the use of selpercatinib and pralsetinib in the first or subsequent lines of treatment. The question of whether to use these selective RET inhibitors alone or with chemotherapy will be answered by the ongoing ARROW and LIBRETT0-431 trials.
We share Jaiswal and Chanana's concern about the development of resistance to these selective RET inhibitors. The G810R/S/C RET mutation has been described in two patients progressing on selpercatinib till date.[6] TPX-0046, a RET/ Sarcome (SRC) inhibitor, is currently being studied in a Phase I trial (NCT04161391) to assess its potential to overcome resistance to RET inhibitors caused by the G810 mutation.[2] However, more studies and trials are necessary to delve into the mechanism of resistance and explore therapies to overcome resistance.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Jaiswal A, Chanana R. Are we there RET? Cancer Res Stat Treat 2022;5:175-6.  [Full text] |
| 2. | Nathany S, Diwan H, Batra U. RET in non-small cell lung carcinoma: A narrative review. Cancer Res Stat Treat 2021;4:702-8. [Full text] |
| 3. | Takahashi M, Ritz J, Cooper GM. Activation of a novel human transforming gene, RET, by DNA rearrangement. Cell 1985;42:581-8. |
| 4. | Batra U, Sharma M, Nathany S, Soni S, Bansal A, Jain P, et al. Biomarker testing in non-small cell lung carcinoma – More is better: A case series. Cancer Res Stat Treat 2020;3:742-7. [Full text] |
| 5. | Gainor JF, Curigliano G, Kim DW, Lee DH, Besse B, Baik CS, et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): A multi-cohort, open-label, phase 1/2 study. Lancet Oncol 2021;22:959-69. |
| 6. | Drusbosky LM, Rodriguez E, Dawar R, Ikpeazu CV. Therapeutic strategies in RET gene rearranged non-small cell lung cancer. J Hematol Oncol 2021;14:50. |
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